Chemoprevention of lung cancers: lessons from CARET, the beta-carotene and retinol efficacy trial, and prospects for the future.

The objective of this paper was to review the strategies for lung cancer chemoprevention. A retrospective assessment of the major findings from the most informative lung cancer chemoprevention clinical trials [alpha-tocopherol (vitamin E), beta-carotene trial and beta-carotene and retinol efficacy trial] was employed. Both trials and many others showed no benefit from what was once the prime candidate for lung cancer chemoprevention, beta-carotene. Furthermore, both trials found that beta-carotene, alone or in combination with vitamin E or retinyl palmitate, increased the incidence of lung cancers and the total and cardiovascular mortality rates. In conclusion, design, conduct, documentation, relationships with participants, and preparedness for unexpected findings are all important for chemoprevention research. Trials are necessary to test inferences from observational epidemiology and animal models. Multiple classes of promising agents are available for evaluation and for eventual randomized trials.